Crystalline polymorphism impacts many properties (stability, melting point, hardness, solubility, etc.) and applications of pharmaceutical agents, therefore detailed analysis of pharmaceutical's polymorphism and development of new approaches to study this phenomenon are still the long-term objectives aims in pharmaceutical science and industry. Many significant advances have been made in the structural analysis of polymorphs that have led to successful pharmaceutical applications. On the other hand, the nature of polymorphism on the modern molecular/atomic/electronic level remains unclear in many respects. In particular, differences in crystal structure related to polymorphism can be ascribed to intermolecular (interatomic) interactions, but until recently, only theoretical descriptions of such interactions existed, and in most cases corresponding conclusions were made only on the basis of 3D-crystal structure pattern. In the present Project we propose experimental investigation and new quantitative evaluation of the effects of intermolecular interactions (including their energies) in crystals, based on the electron density distribution obtained from X-ray diffraction data, and new approach to its analysis based on the experimental electron density topology study. The specific aims of this project are: [unreadable] * To grow crystals of polymorphs of pharmaceutical compounds using different crystallization techniques. [unreadable] * To use high-resolution X-ray diffraction data to study electron density distribution in these polymorphs and to estimate their important properties (including energetic ones) directly from diffraction data. [unreadable] * To quantify interatomic (intermolecular) forces and partial energies that cause polymorphism using new approach - analysis of the electron density topology and its characteristics. [unreadable] * To develop and test new electronic approach for further analysis of known and new pharmaceuticals, and to get some insight on relation between polymorphs electronic structure, stability and bioactivity. [unreadable] We plan to grow polymorphs of five known pharmaceutical/bioactive compounds: acetaminophen, phenobarbital, diclofenac acid, glycine and thalidomide. Because properties, crystallization conditions, and crystal structures for these compounds are well documented, we have ample baseline data for comparison of our new results with known data, that will allow to use our approach in studies of new Pharmaceuticals. [unreadable] [unreadable] [unreadable]